HRR: ADH and RAAS Flashcards
What generates ADH? Where is it released from?
Synthesized in the anterior hypothalamus and secreted from the posterior pituitary
Describe the structure of ADH
A cyclic peptide containing a disulfide bond between two cysteine residues
Describe ADH biosynthesis
Begins as a prohormone consisting of biologically active hormone attached to neurophysin II and copeptin. It is cleaved within the secretory granule, becoming active.
What is neurophysin II?
A carrier protein important for processing and packaging ADH into the secretory granule, and is also important for ATP-dependent transport of ADH down the neurohypophysis tract
How is ADH metabolized?
By the liver and kidney via reduction of the disulfide bond and cleavage of peptide chain
What is the plasma half-life of ADH?
About 10 mins
What are the two ADH receptors?
V1 and V2
What kind of receptor is V1a?
Gq coupled
What does V1a receptor do?
Allow ADH to cause contraction of vascular smooth muscle
What does V1b receptor do?
Promotes ACTH secretion
Where are V2 receptors found?
The renal collecting duct system
What kind of receptor is V2?
Gs coupled
What side of the membrane are V2 receptors on?
The basolateral membrane aka the capillary side of principal cells
How does ADH binding to V2 impact water balance?
More aquaporin channels are inserted on the apical/luminal side of the cell, allowing the collecting duct to become more permeable to water and causing us to retain water. The urine becomes more concentrated.
What is the main mediator of ADH action?
Aquaporin 2
What are osmo sensitive neurons?
Neurons in the anterior hypothalamus that monitor blood osmolality
What do osmoreceptor cells do when blood osmolality is high?
They synapse with ADH neurons via acetylcholine to lead to ADH secretion. They also cause us to be thirstier to take in more water.
How does ADH impact urine concentration?
Makes it more concentrated by allowing us to retain water
What inhibits ADH secretion?
Low blood osmolality
What solutes do osmoreceptors respond to?
Only those that are effective osmoles. Mostly Na+!
Describe hemodynamic input as a stimulus for ADH.
Low BP will release ADH, but it has to be a pretty significant change. It isn’t a directly linear relationship!
Someone has hypoosmolality and volume depletion. Will ADH be secreted?
Yes! When faced with conflicting signals, volume wins
What are some stimuli that increase ADH secretion?
Vomiting, nausea, pain, motion sickness
What does ang II do to ADH secretion?
Ang II stimulates and sensitizes osmoreceptors, leading to increased ADH release
What does alcohol do to ADH secretion?
Effective inhibition of ADH
What does nicotine do to ADH secretion?
Induces it
Describe how diabetes insipidus impacts ADH.
It causes an inability to make or respond to ADH. As a result, we cannot hold onto water and have lots of dilute urine. This also causes people to be super thirsty.
What is central DI?
Damage or destruction of portions of the posterior pituitary prevent ADH secretion
What can treat central DI?
Desmopressin
What is nephrogenic DI?
Kidneys aren’t responding to ADH
What can cause nephrogenic DI?
Mutations in V2 receptors, kidney injury, different drugs (lithium!)
What quantifies diabetes insipidus?
Excess loss of 3L of water per 34 hours
What is SIDAH?
ADH secretion is inappropriately increased; this leads to water retention and euvolemic hyponatremia (no physical exam findings but lab value of low sodium). Has many causes.
What are some symptoms of SIDAH?
Nausea, headache, lethargy, convulsions, coma
